Diarrhea and wasting are relatively common features of AIDS. The cause of gastrointestinal dysfunction may be opportunistic infections (including chronic viral, mycobacterial or parasite infections), bacterial overgrowth, or an immune regulatory defect resulting in systemic stimulation from luminal antigens. Prior studies from our laboratory have been designed to detect enteric pathogens in patients with AIDS and patients at risk for HIV infection. The results showed that about half of AIDS patients with diarrhea had a likely enteric pathogen, the most common being cryptosporidia. The present proposal represents an extension of our prior work with an attempt to characterize "AIDS enteropathy" defined as diarrhea and wasting in the absence of a recognized enteric pathogen. This proposal takes advantage of new collaborative opportunities for studies of epidemiology, immunology, pathology and gastroenterology. The AIDS clinic will serve as the source of clinical material. Three funded projects permit systematic evaluations at six month intervals of 2000-3000 patients/year with HIV infection including 200-300 with AIDS. These patients will serve as the cohort for longitudinal studies to define the incidence and prevalence of diarrhea and wasting. The results will be correlated with disease stage, risk category and immunological assessment. Patients who have the "diarrhea wasting syndrome" will undergo microbiological studies using selective techniques based on our prior work. Patients with no likely enteric pathogen using noninvasive techniques will be classified as "AIDS enteropathy". The major project is designed to define the morphology and immunopathology of the gut in patients with "AIDS enteropathy". A broad goal will be to determine if AIDS enteropathy is a discrete entity that can be ascribed to HIV infection or consequences of a superimposed process such as a viral, mycobacterial or parasitic infection that is not detected with noninvasive screening tests. This work will include patients with diarrhea-wasting as defined above and controls without diarrhea who are matched for disease stage. The studies will include: 1) ultrastructural changes, 2) studies for microbial agents using electron microscopy, special stains, in situ hybridization, and culture and 3) studies of immunopathology including possible autoimmune features and 4) comparisons of circulating and secretory immunoglobulin.